Spectrophotometric Evaluation of Urethane Acrylate
Based Pigment Colour Stability
Jaqueline Vieira1,2*, Natasha Maurmann3,4, Janio Venturini1,2, Patricia Pranke3,4,5, Carlos Pérez Bergmann1,2
1Post-Graduate Program in Mining, Metallurgical and Materials Engineering, Laboratory of Ceramics
(LACER), Universidade Federal do Rio Grande do Sul (UFRGS), Av. Osvaldo Aranha 99, Porto Alegre,
2Department of Industrial Engineering, School of Engineering, Universidade Federal do Rio Grande do
Sul (UFRGS), Avenida Osvaldo Aranha, 99. Porto Alegre, 90035-190, Brazil
3Hematology and Stem Cell Laboratory, Faculty of Pharmacy, Universidade Federal do Rio Grande do
Sul (UFRGS). AvenidaIpiranga, 2752/304G, Porto Alegre, 90610-000, Brazil4 Post- graduate Program in
Physiology, Universidade Federal do Rio Grande do Sul (UFRGS), AvenidaSarmentoLeite, 500/sala PPG
Fisiologia, Porto Alegre, 90050-170, Brazil
4Post-graduate Program in Physiology, Universidade Federal do Rio Grande do Sul (UFRGS),
AvenidaSarmentoLeite, 500/sala PPG Fisiologia, Porto Alegre, 90050-170, Brazil
5Stem Cell Research Institute, Porto Alegre, 90020-010, Brazil
Jaqueline Vieira, Department of Industrial Engineering, School of Engineering, Universidade Federal do Rio Grande do Sul
(UFRGS), Avenida Osvaldo Aranha, 99, Porto Alegre, 90035-190, Brazil; E-mail:
Received: May 20, 2020; Accepted: June 03, 2020; Published: June 17, 2020
Jaqueline Vieira, Natasha Maurmann, Janio Venturini, Patricia Pranke et al. (2020) FProduction and Characterization of
Nanoparticles Coated with PCL for Biomedical Applications. SOJ Mater Sci Eng 7(1): 1-6. DOI: http://dx.doi.org/10.15226/sojmse.2019.00158
Currently, magnetic nanoparticles are widely studied with regard
to their application in cancer treatment. This study aims to show a
straightforward strategy for the production of Fe3O4 nanoparticles
(NPs) with biocompatible surface modifications with polycaprolactone
(PCL) for biomedical purposes. The effects of the polymer coating on
the properties of magnetite were evaluated. Crystallinity, morphology,
composition, hydrodynamic size and magnetic properties of the
produced nanoparticles were analysed via X-ray diffractometry (XRD),
Transmission Electron Microscopy (TEM), Fourier-Transform Infrared
Spectroscopy (FTIR), Dynamic Light Scattering (DLS) and Vibrating
Sample Magnetometry (VSM), respectively. The proposed method
produced nanoparticles of magnetite with an average size between
9 and 11 nm, with spherical morphology and superparamagnetic
properties. Magnetization values were not compromised even when
the highest amount of polymer was used in the surface modification.
On the other hand, the coating resulted in the decrease of the
hydrodynamic size of the composites, indicating greater colloidal
stability when the polymer was present. The obtained nanoparticles
showed maintenance of significant superparamagneticbehavior, even
in the presence of PCL on their surface. This phenomenon would allow
for their application as a further optimized vector in hyperthermia
cancer treatment, controlled drug delivery and resonance imaging.
Keywords: Nanoparticles; Magnetite;PCL; Cancer; Hyperthermia
The term ‘cancer’ refers to a group of more than 100 diseases
that are triggered by a disordered growth of cells, with the
formation of tumours. Therefore, the treatment of this condition
is based on the prevention the multiplication of these cells and/
or the removal of the tumour; in order to improve the treatment,
more than one tool can be combined. Many types of cancers
can be reversed when caught early and treated effectively, with
a possible decrease in the mortality rate of 30 to 50% [1,2,3,4].
Chemotherapy is one of the most common methods used for
treating cancer. It consists of using chemical drugs systematically
throughout the body to prevent the proliferation of cancer
cells and to kill them. However, cancer cells are not the only
ones with accelerated growth in the human body. Due to the
unspecific delivery, healthy cells are also subjected to the effects
of the drug as well. This phenomenon brings about several side
effects, such as nausea, hair loss and immune suppression [5,6].
Besides these factors, the indirect delivery system decreases the
amount of the remedy that actually gets to the tumor, reducing
the therapeutic efficacy. To prevent this from happening, studies
are being conducted in order to make drug delivery systems
(DDS) that are cell-specific, optimizing the treatment .
These systems present several advantages: protecting the drug,
releasing it in the location of interest, allowing the use of roughly
100 times less compound and reducing the side effects .
Another type of cancer treatment that has been widely studied is
hyperthermia. Because cancer cells are more sensitive to higher temperatures, when the tissue containing the tumor is submitted
to hyperthermia treatment, these specific cells suffer more
damage or are killed . Among the several nanoparticles that
can be used for biomedical applications, magnetic materials are
very attractive (MNP), especially those with superparamagnetic
characteristics, as they are used in diagnosis, as contrasting agents
for magnetic resonance imaging (MRI) and in the treatment of
several conditions . Iron(II) and (III) oxide (Fe3O4) MNPs
appear to have the highest potential for use in cancer treatment
as they are biocompatible, superparamagnetic and easy to
functionalize. Furthermore, they can incorporate drugs and are
easily separated from the solution by magnetic recovery, which
prevents the degradation of the NP elements, including the drug.
Moreover, this magnetic property allows for the use of these MNPs
as targeted DDSs, using a magnetic field gradient to guide them to
specific spots in the human body . Their use as thermossed
for hyperthermia is linked to their ability of generating local
heat under alternating magnetic fields, as results of Néel and
Brownian relaxations and hysteresis loss in this condition [9,12].
However, morphology, dispersibility and the hydrodynamic
size of the nanoparticles are important and influence their use
in biomedical applications [5,13]. Moreover, these MNPs have
already been approved by the Food and Drug Administration of
the United States . For the purpose of biomedical applications,
even though the MNPs of Fe3O4 (magnetite) have the previously
aforementioned advantages, some modifications may be required
for the particles to stay longer in the body and be more biostable.
One of the most used approaches is the use of polymers as surface
modifiers. Polycaprolactone (PCL) is a promising candidate for
this function. It is a biocompatible and biodegradable polymer
due to its being susceptible to enzymatic degradation, and is bioresorbable. PCL has already been approved by the FDA and it
has good solubility in common organic solvents [15-18]. Withal,
PCL has several advantages against other polymers as it is highly
permeable to various drugs, can easily form copolymers and
its degradation does not generate an acid environment in the
body . The greatest challenge remains in finding a cheap
and large-scale synthesis method that produces these MNPs
with satisfactory sizes with adequate surface modifications and
which ensure stability under physiological conditions, more
importantly, without compromising properties such as their
magnetism, but having steps with minimal damage to the surface
modifiers and active principles, thereby enabling them to be used
as DDSs and vehicles for hyperthermia [4,8,20]. The present work
aims to synthesize, through a simple method, magnetite MNPs
with surface modification by PCL, with a smooth recovery process
that alter as little as possible the surface polymer and possible
drugs that may be used. This would improve their performance in
physiological conditions without suffering significant loss in the
Ferrous chloride tetrahydrate (FeCl2•4H2O ≥99%), ferric
chloride hexahydrate (FeCl3•6H2O 97%) and PCL bovine
serum albumin (BSA) were purchased from SIGMA-ALDRICH,
ethyl acetate and isopropyl alcohol from NEON, acetone from REATEC and ammonium hydroxide from VETEC. All used
chemicals were of AR grade unless otherwise specified, and all
the aqueous solutions were prepared using deionized water
from a MilliQ filtration system. Synthesis of Fe3O4@PCL NPs
Magnetite nanoparticles were synthesized by co-precipitating
Fe(II) and Fe(III) salt precursors in a basic medium. FeCl2•4H2O
and FeCl3•6H2O (1:2 molar ratio of Fe3+/Fe+2) were dissolved in
40 mL of deionized water. A solution of ammonium hydroxide
(25% wt NH4OH) was rapidly added dropwise until pH reached
11 under vigorous stirring and temperature of 60°C for 1 hour.
The produced material was magnetically separated and washed
with deionized water and isopropyl alcohol several times. The
black rump was resuspended in deionized water. The PCL was
dissolved in a stock solution of acetone and ethyl acetate (4:1)
under vigorous stirring at 50°C. The MNPs were subjected to
surface modification in four different amounts of the polymer
(0, 20, 40, 60 and 80 mg, with the sample named after these
amounts as Am0, Am20, Am40, Am60 and Am80) by an oil-inwater
emulsion solvent-evaporation modified method. The
solution carrying PCL was added dropwise in the water solution,
holding the MNPs under vigorous stirring at 50°C for one hour for
the polymer to interact with the nanoparticles and the solvents
evaporate. Following this, the MNPs were collected with a magnet,
washed several times with deionized water and isopropyl alcohol,
resuspended in deionized water, submitted to ultrasound for 15
minutes, magnetically separated once again, and finally dried in
an oven at 50°C for 24 hours.
Powder X-ray diffractometry (XRD) was performed to analyse
the formation of the spinel phase in an X’Pert MPD Phillips
equipment with Cu-Kα radiation (1.54184 Å). Fourier transform
infrared spectrometry (FTIR) was used to verify the presence
of the polymer. Assays were performed using an IRAFFINITY 1
(Shimadzu) spectrometer. Spectra were recorded in the range
between 4000 and 500 cm-1, with samples diluted in KBr. The
magnetic properties were characterized using a vibrating
sample magnetometer (VSM, MicroSense) at room temperature.
Transmission electron microscopy (TEM) was used to observe
crystallite morphology and size. A Joel JEM device operating
at 80kV was used, with the samples placed in a carbon-coated
copper grid. Dynamic light scattering (DLS) measurements
were performed to obtain the average hydrodynamic size of the
nanoparticles using a Zetasizer Nano Zs (Malvern). The MNPs
were diluted to a concentration of 0.1 mg.mL-1 with deionized
The XRD results show the diffraction patterns of the produced
MNPs, with the expected (220), (311), (400), (422), (440) and
(511) reflections corresponding to the crystalline structure of
Fe3O4 cubic spinel(Figure 1). Thus, the patterns confirm the
successful production of the desired material. Furthermore, the
Figure 1: XRD patterns of Fe3O4 nanoparticles produced with and without PCL.
Figure 2: FTIR absorption spectra of the different produced MNPs, with stripes indicating important bands.
Figure 3: Magnetization curves of the MNPs with different amounts of polymer, measured via VSM.
addition of PCL did not affect the diffractograms, thus indicating that the crystalline structure of magnetite is maintained after the
addition of the polymer.FTIR data shows the existence of absorption bands that correspond to the presence of the polymer(Figure 2).
The most striking band is seen at approximately 1726 cm-1, which corresponds to the stretching of the carbonyl (C=O) of the PCL ester
group, confirming the surface modification by the polymer . Beside this, other less expressive bands, such as those corresponding
to the symmetrical and asymmetrical stretches of CH2 bond (2944 and 2863 cm-1), OH bond stretch (2300 cm-1), CH group stretching
in CH2 (1487 cm-1), the CO and CC double bonds (1268, 1160 cm-1) and COC asymmetric stretch (1240 cm-1) were also found . It
is worth mentioning that the markings were made next to each band in order not to hide them. The intensity of the bands is also directly
linked to the added concentration of PCL, which could be linked to an increased presence of the polymer. The results of the VSM assays
show the magnetic properties of treated and untreated MNPs(Figure 3). It is worth noting that all hysteresis curves display negligible
remanence (Mr) and coercivity (Hc), proving that MNPs have superparamagneticbehavior. Transmission electron microscopy was
used to verify the morphology of the MNPs. (Figure 4) shows that the nanoparticles have spherical shapes with good crystallinity, in
agreement with the XRD results and with the literature that also used polymers as a surface modifier [2,23-25]. A certain regularity
among the NP sizes (around 10 nm) was also observed in (Figure 5). The hydrodynamic diameters of the MNPs are described in (Table
1). The values obtained by DLS showed a decrease in size of the particles containing the polymer, with a reduction of approximately
57% when comparing the bare NPs to the Am80 sample.
Figure 4: TEM images of a) Am0; b) Am20; c) Am40; d) Am60; e) Am80
Figure 5: Histogram data curve fitting on diameter of MNPs a) Am0; b) Am20; c) Am40;d) Am60; e) Am80
Table 1. Hydrodynamic sizes of the MNPs measured by DLS
Hydrodynamic size (nm)
466.50 ± 13.47
336.20 ± 31.48
290.18 ± 7.72
282.40 ± 10.33
267.78 ± 6.01
As shown in the XRD results (Figure 1), the reflections
corresponding to magnetite are all present, indicating the
crystalline structure of Fe3O4 cubic spinel and thereby proving
the effectiveness of the coprecipitation method in producing
these nanoparticles [2,26]. As the present experiment was not
carried out under nitrogen atmosphere, oxidation could occur,
converting the material into maghemite. However, the black
colour of the final material, as opposed to of an ochre colour,
and the XRD reflections are good indications of the composition,
consisting mostly of magnetite [4,27]. Unlike that which was
reported by only magnetite reflections were observed in the
XRD data, without clear signs of the polymer. This phenomenon
may have occurred due to the lower concentrations of the
polymer used to make the surface modification in this study, as
the intention in the present work was to preserve as much as
possible the magnetic properties for a possible further optimized
hyperthermia. In the FTIR data (Figure 2), bands corresponding
to the polymer bonds increased in intensity as the polymer
concentration increased, while being absent in the sample of bare
ferrite, AM0, proving that one can adapt the particle synthesis
towards the desired composition via the proposed method .
The presence of these bands also indicates that the magnetic
recovery used in the synthesis did not affect the polymer. The
superparamagneticbehavior can be observed in their M-H
curves, as in (Figure 3), proving that MNPs could be used for
biomedical applications as thermoseeds for local cancer therapy
and diagnosis. In (Figure 3), a slight increase in magnetization
can be noticed in the samples that are surface-modified by PCL,
contrary to the findings of some works, in which the presence
of the polymer resulted in a decrease in the magnetization of
the NPs [4,20]. However, the coating does not always limit the
entire surface of the MNP to the point of reducing magnetization
. Sometimes, the modification may result in surface changes
that facilitate the ordering of the moments, or even preserve
the magnetite phase, reducing the oxidation to maghemite
, events that may have occurred in this work. Either way,
the maintenance of magnetic properties can be used to reduce
the amount of MNPs that would be needed to induce a good
response to the applied magnetic field, generating satisfactory
heat production and targeting in the treatment of tumours by
hyperthermia and controlled DDS, resulting in lower cytotoxic
risks . Moreover, a decrease in magnetization of the sample
with the highest PCL concentration (AM80) is observed, which
could be the combination of the result of the studies above, where
it could still have a higher degree of magnetite and/or organized
moments than the pure MNPs. The amount of polymer should
result in a smaller fraction of magnetite in the final NP, decreasing
the magnetization in relation to the other treated samples [26-
28]. TEM images, (Figure 4), do not allow for the visualization of
the polymeric layer, a fact that has also been reported by some
authors who used PCL or even other polymers and organic coatings
in low concentrations. Instead, the modification is confirmed by
the FTIR data, where PCL bands could be easily discerned, as
was also carried out in this work [29,2,23,26,25]. Nanoparticles
with constant sizes, size distribution, and shape were observed,
(Figure 5). This morphological uniformity is crucial considering
that the successful application of these nanoparticles depends on
their morphology . Other characteristics that influence the
biomedical applications of MNPs are their colloidal stability and
their size when suspended . The decrease in hydrodynamic size
of those nanoparticles containing more polymer, presented in the
DLS analysis in (Table1), evidences an increase in dispersibility
caused by the surface modification with PCL, testifying the
greater stability of the MNPs in the presence of the polymer. The
difference between sizes found via DLS and TEM data likely occurs
due to the presence of a hydration layer around the MNPs in the
DLS configuration as this technique measures the size of particles
in colloidal suspension combining the obtained results, it is clear
that these MNPs are promising materials for biomedical purposes
that utilize their magnetic responses in cancer treatment[1,2].
In this study, magnetite nanoparticles with surface
modifications by PCL were successfully synthesized by a simple
method. The magnetic separation used in the method did not
cause damage to the polymer on the surface. The particles
present spherical shapes, general size within the 10 nm range,
and regular distribution. The bands of the polymer were stronger
as the concentrations increased, as shown by the FTIR data. The
hysteresis curves presented the superparamagneticbehavior of
the MNPs, even in the presence of the polymer on the surface,
indicating the possibility of them serving as thermoseeds for
general hyperthermia. This character would also serve to target
the MNPs using a magnetic field gradient for local hyperthermia
and controlled drug release. The results allow for their use in
these treatments without the need of higher concentrations
of the nanoparticles in order to obtain a good response to the
The authors would like to acknowledge the support of the
Ministry of Science, Technology, Innovation and Communication
(MCTIC), the National Council of Technological and Scientific
Development (CNPq) Coordination for the Improvement of Higher
Education Personnel (CAPES), and the Research Foundation of
the State of Rio Grande do Sul (FAPERGS).
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